The aim of this project is to produce a book-length account of systematic attempts to encourage the rational use of therapeutics in late 20th and early 21st century American medicine. The grant will provide for part-time research funding to support the PI for three years of manuscript preparation and final archival research during this period. Nearly all contemporary proposals to improve the quality of US health care while cutting its costs depend on the premise of therapeutic equivalence: if drugs have identical efficacy one medicine (cheaper, safer) might be substituted for another (costlier, riskier) to produce more effective care overall. On closer examination, the science of similarity that underpins rational pharmaceutical use has been methodologically, clinically, and politically contested for the past half-century, and the results f these deliberations continue to influence current health policy options. The manuscript will narrate the history of three related attempts to establish and utilize notions of therapeutic equivalence in late 20th century America: (1) the scientific, regulatory, and political conflicts tat arise in trying to ensure generic equivalence between chemically identical brand-name and generic prescription drugs, (2) the private and public contests that emerge in defining the boundaries of therapeutic substitution of one drug for another within a therapeutic class of molecularly-different but clinically similar 'me too' drugs, and (3) the heterogeneous legacy of programs to guide physicians towards more rational prescribing of therapeutically equivalent compounds to favor safer and less expensive therapeutic agents. This work will represent the first history of rational pharmaceutical use in American medical practice and health policy, and it has great potential to inform ongoing national and international conversations on health care reform moving forwards.